rebaudioside-a and Diabetes-Mellitus--Type-2

Rebaudioside A, a steviol glycoside, is deglycosylated by intestinal microflora prior to the absorption of steviol and conjugation to steviol glucuronide. While glucose-lowering properties are observed for rebaudioside A in mice, they have been attributed to the metabolites steviol and steviol glucuronide. We aimed to characterize the pharmacokinetic and pharmacodynamic properties of rebaudioside A and its metabolites in patients with early-onset type 2 diabetes mellitus (T2DM).. This randomized, placebo-controlled, open-label, two-way crossover trial was performed in subjects with T2DM on metformin or no therapy at the University Hospitals Leuven, Belgium. Following oral rebaudioside A (3 g), plasma concentrations of rebaudioside A, steviol and steviol glucuronide were determined. The effect on glucose homeostasis was examined by an oral glucose tolerance test (OGTT) performed 19 h following rebaudioside A administration, i.e. the presumed time of maximal steviol and steviol glucuronide concentrations. The primary pharmacodynamic endpoint was the difference in area under the blood glucose concentration-time curve during the first 2 h of the OGTT (AUC. Rebaudioside A is readily absorbed after oral administration and metabolized to steviol and steviol glucuronide. However, no effect on glucose nor insulin or C-peptide excursion was observed during the OGTT at the time of maximal metabolite concentrations. Thus, no antidiabetic properties of rebaudioside A could be observed in patients with T2DM after single oral use.. Registered on ClinicalTrials.gov (NCT03510624).

Topics: Animals; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glucose; Glucuronides; Homeostasis; Male; Mice

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Topics: Adult; Area Under Curve; Aspartame; Beverages; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Male; Middle Aged; Stevia; Sucrose; Sweetening Agents; Treatment Outcome; Young Adult

This trial evaluated the effects of 16 weeks of consumption of 1000mg rebaudioside A (n=60) a steviol glycoside with potential use as a sweetener, compared to placebo (n=62) in men and women (33-75 years of age) with type 2 diabetes mellitus. Mean+/-standard error changes in glycosylated hemoglobin levels did not differ significantly between the rebaudioside A (0.11+/-0.06%) and placebo (0.09+/-0.05%; p=0.355) groups. Changes from baseline for rebaudioside A and placebo, respectively, in fasting glucose (7.5+/-3.7mg/dL and 11.2+/-4.5mg/dL), insulin (1.0+/-0.64microU/mL and 3.3+/-1.5microU/mL), and C-peptide (0.13+/-0.09ng/mL and 0.42+/-0.14ng/mL) did not differ significantly (p>0.05 for all). Assessments of changes in blood pressure, body weight, and fasting lipids indicated no differences by treatment. Rebaudioside A was well-tolerated, and records of hypoglycemic episodes showed no excess vs. placebo. These results suggest that chronic use of 1000mg rebaudioside A does not alter glucose homeostasis or blood pressure in individuals with type 2 diabetes mellitus.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Diterpenes, Kaurane; Double-Blind Method; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Lipids; Male; Middle Aged; Placebos; Sweetening Agents

Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resulting from deficits in insulin secretion or insulin function. This disease usually links with various psychological problems such as anxiety and cognitive dysfunctions. Stevia (Stevia rebaudiana Bertoni) is a natural and healthy substitute sweetener for sugar and artificial sweeteners. It has become essential for human diets and food manufacturers. The aim of this research was to investigate the effects of Stevia and Nano-stevia on the regulation of anxiety and memory processes in male diabetic rats. The elevated plus-maze (EPM) test-retest procedure was used to assess anxiety and memory in male diabetic rats. The findings exhibited that induction of diabetes caused a distorted cellular arrangement in the liver tissue of male rats. On the other hand, intra-gastrically administration of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) indicated a normal appearance in the liver tissue of male diabetic rats. Moreover, induction of diabetes caused the augmentation of blood glucose, reduction in time spent in%open-arm time (%OAT) on the test day, and enhancement of%OAT on the retest day. Therefore, induction of diabetes in rats produced hyperglycemia, anxiogenic effect, and memory impairment and these responses were reversed by drug treatment. Furthermore, intra-gastrically application of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) reversed the hyperglycemia, anxiogenic effect, and memory impairment in male diabetic rats. Interestingly, Nano-Stevia exhibited the highest significant response rather than Stevia. In conclusion, the results of this research suggested the beneficial properties of Stevia and particularly Nano-Stevia on inducing anti-diabetic effects, anxiolytic behavior, as well as memory improvement in male diabetic rats.

Topics: Animals; Anxiety; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Male; Memory Disorders; Plant Extracts; Rats; Stevia; Streptozocin; Sweetening Agents

Diabetes mellitus (DM) is a common chronic medical condition characterized by hyperglycemia resulting from abnormal insulin functionality, of which type 2 DM (T2DM) is the predominant form. An inulin-type fructan, denoted as SRRP, was obtained from

Topics: Animals; Diabetes Mellitus, Type 2; Fructans; Hypoglycemic Agents; Inulin; Mice; Stevia

Type 2 diabetes mellitus (T2DM), a growing health problem worldwide, is a metabolic disorder characterized by hyperglycemia due to insulin resistance and defective insulin secretion by pancreatic β-cells. The skeletal muscle is a central organ that consumes most of the insulin-stimulated glucose in the body, and insulin resistance can damage muscles in T2DM. Based on a strong correlation between diabetes and muscles, we investigated the effects of stevia extract (SE) and stevioside (SV) on the skeletal muscle of diabetic db/db mice.. The mice were administered saline, metformin  (200 mg/kg/day), SE (200 and 500 mg/kg/day), and SV (40 mg/kg/day) for 35 days. During administration, we checked the levels of fasting blood glucose twice a week and conducted the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). After administration, we analyzed serum biochemical parameters, triglyceride (TG), total cholesterol (TC), insulin and antioxidant enzymes, and the cross-sectional area of skeletal muscle fibers of db/db mice. Western blots were conducted using the skeletal muscle of mice to examine the effect of SE and SV on protein expression of insulin signaling, mitochondrial function, and oxidative stress.. SE and SV administration lowered the levels of fasting blood glucose, OGTT, and ITT in db/db mice. The administration also decreased serum levels of TG, TC, and insulin while increasing those of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Interestingly, muscle fiber size was significantly increased in db/db mice treated with SE500 and SV. In the skeletal muscle of db/db mice, SE and SV administration activated insulin signaling by increasing the protein expression of insulin receptor substrate, Akt, and glucose transporter type 4. Furthermore, SE500 administration markedly increased the protein expression of AMP-activated protein kinase-α, sirtuin-1, and peroxisome proliferator-activated receptor-γ coactivator-1α. SV administration significantly reduced oxidative stress by down-regulating the protein expression of 4-hydroxynonenal, heme oxygenase-1, SOD, and GPx. In addition, SE500 and SV administration suppressed the expression of apoptosis-related proteins in the skeletal muscle of db/db mice.. SE and SV administration attenuated hyperglycemia in diabetic mice. Moreover, the administration ameliorated insulin resistance by regulating mitochondrial function and oxidative stress, increasing muscle fiber size. Overall, this study suggests that SE and SV administration may serve as a potential strategy for the treatment of diabetic muscles.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glutathione Peroxidase; Hyperglycemia; Insulin; Insulin Resistance; Mice; Mitochondria; Muscle, Skeletal; Oxidative Stress; Stevia; Superoxide Dismutase

In diabetes, in parallel to hyperglycaemia, elevated serum lipids are also diagnosed, representing a high-risk factor for coronary heart disease and cardiovascular complications. The objective of this study was to unravel the mechanisms that underlie the potential of steviol glycosides (stevioside or rebaudioside A) administered at two doses (500 or 2500 mg/kg body weight for 5 weeks) to regulate lipid metabolism. In this paper, the expression of selected genes responsible for glucose and lipid metabolism (Glut4, Pparγ, Cebpa, Fasn, Lpl and Egr1) in the peripheral tissues (adipose, liver and muscle tissue) was determined using quantitative real-time PCR method. It was found that the supplementation of steviol glycosides affected the expression of Glut4, Cebpa and Fasn genes, depending on the type of the glycoside and its dose, as well as the type of tissue, whish in part may explain the lipid-regulatory potential of steviol glycosides in hyperglycaemic conditions. Nevertheless, more in-depth studies, including human trials, are needed to confirm these effects, before steviol glycosides can be used in the therapy of type 2 diabetes.

Topics: Diabetes Mellitus, Type 2; Gene Expression; Glycosides; Humans; Hyperglycemia; Lipid Metabolism; Stevia

Diabetes mellitus (DM) has been considered a major problem because of its related complications and growing incidence worldwide. Testicular dysfunction has become a predominant diabetic complication characterized by impaired reproductive function and testicular damage. Stevia rebaudiana Bertoni has been known for its antioxidant effect on diabetes, inflammation, and obesity. The current study investigates the protective effect of Stevia on diabetic-induced testicular injury.. Sprague Dawley adult male rats were divided into three groups: the control group, the diabetic group, and the diabetic + Stevia group, type 2 diabetes is induced by a high-fat diet (HFD) and a single dose of 35 mg/kg streptozotocin injection. The effects of Stevia were evaluated regarding biochemical, oxidative stress, histopathological and ultrastructural changes, and immunohistochemical expression of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), receptor-interacting serine/threonine-protein kinase 1 (RIPK 1), and caspase 3.. Stevia extract attenuated the diabetic-induced oxidative stress, restored the testicular architecture, and decreased testicular damage, inflammation, necroptosis, and apoptosis by upregulating VEGF and downregulating VCAM 1, RIPK 1, and caspase 3.. The current study highlights the importance of Stevia as an antioxidant anti-inflammatory that ameliorates diabetic-induced testicular injury by modulating oxidative stress, inflammation, necroptosis, and apoptosis.

Topics: Animals; Antioxidants; Caspase 3; Diabetes Mellitus, Type 2; Inflammation; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Rats, Wistar; Stevia; Streptozocin; Vascular Endothelial Growth Factor A

Stevia rebaudiana Bertoni leaf extracts have gained increasing attention for their potential protection against type 2 diabetes. In this study, we have evaluated the possible beneficial effects of Stevia rebaudiana leaf extracts on beta-cells exposed to lipotoxicity and explored some of the possible mechanisms involved.. Extracts, deriving from six different chemotypes (ST1 to ST6), were characterized in terms of steviol glycosides, total phenols, flavonoids, and antioxidant activity. INS-1E beta cells and human pancreatic islets were incubated 24 h with 0.5 mM palmitate with or without varying concentrations of extracts. Beta-cell/islet cell features were analyzed by MTT assay, activated caspase 3/7 measurement, and/or nucleosome quantification. In addition, the proteome of INS-1E cells was assessed by bi-dimensional electrophoresis (2-DE).. The extracts differed in terms of antioxidant activity and stevioside content. As expected, 24 h exposure to palmitate resulted in a significant decrease of INS-1E cell metabolic activity, which was counteracted by all the Stevia extracts at 200 μg/ml. However, varying stevioside only concentrations were not able to protect palmitate-exposed cells. ST3 extract was also tested with human islets, showing an anti-apoptotic effect. Proteome analysis showed several changes in INS-1E beta-cells exposed to ST3, mainly at the endoplasmic reticulum and mitochondrial levels.. Stevia rebaudiana leaf extracts have beneficial effects on beta cells exposed to lipotoxicity; this effect does not seem to be mediated by stevioside alone (suggesting a major role of the leaf phytocomplex as a whole) and might be due to actions on the endoplasmic reticulum and the mitochondrion.

Topics: Antioxidants; Diabetes Mellitus, Type 2; Flavonoids; Humans; Plant Extracts; Stevia

The potentiality of Stevia leaves and turmeric roots as remedies against diabetes mellitus type 2 was tested in this study. Stevia leaves and turmeric roots were extracted with ethanol:water (80:20 v/v) and analyzed by HPLC. Turmeric extract (TUE) was rich in; curcumin, gallic acid, and eugenol. Stevia extract (STE) contained 28 known compounds, including glycosides, aromatic organic acids, and catechin. Fifty rats were divided into five groups (10 rats each); the control group were fed with feed and water ad libitum. Forty rats were injected a single dose of alloxan, then treated with either 10 mg/kg glibenclamide (GLI), 300 mg/kg STE, or 200 mg/kg TUE or water (positive control) through daily gastric oral gavages for 56 days. Treating diabetic rats with TUE significantly reduced serum glucose and glycated hemoglobin down to the negative control levels. Both GLI and STE produced similar but less effective actions. Animals treated with either STE or TUE exhibited reduced levels of liver and kidney markers compared to the negative control, while GLI increased them significantly. It could be concluded that turmeric roots and stevia leaves extracts can be used treatment for type 2 diabetes. PRACTICAL APPLICATIONS: Turmeric roots and stevia leaves extracts may be used as a remedy for type 2 diabetic patients as aiding substituting treatments under medical supervision. The two plant sources can be used as raw materials for the extracts, which can be used under medical supervision as a gradual replacement of the synthetic antidiabetic drugs. These extracts can be used after a preliminary clinical study to determine the dose and frequency of administration. Stevia extract can be incorporated in drinks as a sweetener and drug. Turmeric extract has a bitter taste, so it may be incorporated in some foods such as bread, which is a traditional practice in some kinds of bread in Egypt. But its content in the bread and the acceptability of the taste should be adjusted. Alternatively, this food can incorporate both TUE and STE to get the best biological action and to conceal the bitter taste of turmeric.

Topics: Animals; Curcuma; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Plant Extracts; Rats; Stevia

Topics: Animals; Biomarkers; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Supplements; Diterpenes, Kaurane; Glucosides; Lipid Metabolism; Male; Rats; Rats, Wistar

In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms.. Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured.. T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05).. Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

Topics: Animals; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Male; Oxidative Stress; Physical Conditioning, Animal; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Signal Transduction; Stevia

Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diet, High-Fat; Diterpenes, Kaurane; Female; Glucosides; HEK293 Cells; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Mice, Knockout; Patch-Clamp Techniques; Sweetening Agents; Taste; TRPM Cation Channels

Diabetes mellitus is a chronic disease characterized by abnormal carbohydrate, lipid and protein metabolism due to a lack of insulin or reduced target cell sensitivity to insulin. Stevia rebaudiana is an important source of biochemically active substances with proven anti-diabetic effect. The aim of this study was to determine anti-diabetic effects of the low dose of stevioside in NMRI Haan mice. Aqueous stevioside solution (20mg/kg body weight) was administered by oral route of administration. Anti-diabetic effect of stevioside was estimated by oral glucose tolerance test, adrenaline test after a 10day stevioside treatment, and alloxan induced hyperglycaemia in mice (two experimental groups, 10day stevioside treatment before and after alloxan administration). Aqueous stevioside solution prevented significant increase in glycaemia in oral glucose tolerance test (9.22±1.13 to 9.85±1.32mmol/l, P<0.05), and not in adrenaline test. Significant difference in glycaemia was detected in mice pre-treated with saline and stevioside in alloxan induced hyperglycaemia (saline 23.32±2.14, stevioside 14.70±4.95mmol/l, P<0.05). In mice pre-treated with stevioside, smallest β cells loss was found compared to other alloxan treated groups. Preserved normal cytoarchitectonic arrangement in islets was detected. Based on the given results we presume there exist a potential therapeutic use of low dose stevioside in diabetes.

Topics: Alloxan; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diterpenes, Kaurane; Glucose Tolerance Test; Glucosides; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Mice; Phytotherapy; Plant Extracts; Stevia

The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. India shelters the highest number of diabetics and is thus known as the 'Diabetes Capital of the World'. The chemical management of diabetes has side effects and hence the present study was undertaken to assess the hypoglycaemic and hypolipidaemic effect of Stevia rebaudiana in patients with type 2 diabetes, non-insulin dependent diabetes mellitus (NIDDM). Its nutritional composition and use as a sweetener substitute were also assessed.. Chemical analysis of dried Stevia leaf powder revealed it to be a nutritious herb with a good iron and fibre content. Intervention trials in diabetics revealed that it significantly lowered fasting and post-prandial blood glucose levels. The serum triglycerides and VLDL-C levels were also significantly reduced.. Hence it can be said that Stevia can safely be used as an anti-diabetic herb, as a sweetener substitute and may help to prevent cardiovascular diseases in patients with long-standing diabetes. © 2016 Society of Chemical Industry.

Topics: Blood Glucose; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; India; Male; Plant Extracts; Plant Leaves; Powders; Stevia; Sweetening Agents; Triglycerides